Cho A K, Hiramatsu M, Schmitz D A, Vargas H M, Landaw E M
Department of Pharmacology, University of California, Los Angeles School of Medicine.
J Pharmacol Exp Ther. 1993 Mar;264(3):1401-5.
Phenylcyclohexyldiethylamine (PCDE) is an analog of phencyclidine with low affinity for the N-methyl-d-aspartate receptor that is metabolized to an active monoethyl derivative, phenylcyclohexylethylamine (PCE). In a pharmacokinetic analysis of the ataxia response of rats to i.p. administered PCDE and PCE, ataxia intensity was determined together with plasma and cerebrospinal fluid concentrations of the drugs. The role of PCE as the active metabolite of PCDE was assessed quantitatively by correlating the response with both the plasma and cerebrospinal fluid drug levels. Increased PCE concentrations in the cerebrospinal fluid and plasma were associated with increased ataxia response when either PCDE or PCE was the administered drug. However, the concentration-response curves did not superimpose and the curve after PCDE was shifted to the left of that after PCE, suggesting that PCDE was contributing an effect not accountable by PCE concentration. This apparent potentiation must involve an interaction at sites other than the N-methyl-daspartate receptor. In the analysis of the behavior responses, PCDE was found to induce a greater backpedalling response which has been attributed to interaction with dopamine or serotonin systems, suggesting that other transmitter systems may contribute to the overall ataxia response.
苯基环己基二乙胺（PCDE）是苯环己哌啶的类似物，对N-甲基-D-天冬氨酸受体亲和力较低，可代谢为活性单乙基衍生物苯基环己基乙胺（PCE）。在一项关于大鼠对腹腔注射PCDE和PCE的共济失调反应的药代动力学分析中，测定了共济失调强度以及药物在血浆和脑脊液中的浓度。通过将反应与血浆和脑脊液中的药物水平进行关联，定量评估了PCE作为PCDE活性代谢物的作用。当给予PCDE或PCE时，脑脊液和血浆中PCE浓度的升高与共济失调反应的增强相关。然而，浓度-反应曲线并未重叠，且PCDE后的曲线向PCE后的曲线左侧偏移，这表明PCDE产生了一种不能用PCE浓度来解释的效应。这种明显的增效作用必定涉及N-甲基-D-天冬氨酸受体以外位点的相互作用。在行为反应分析中，发现PCDE会引发更大的倒退反应，这归因于与多巴胺或5-羟色胺系统的相互作用，表明其他递质系统可能对整体共济失调反应有影响。
